Influencing factors of hospitalization cost of hypertension patients in traditional Chinese medicine hospitals.

Objectives: This study aimed to analyze the influencing factors of hospitalization cost of hypertensive patients in TCM (traditional Chinese medicine, TCM) hospitals, which can provide a scientific basis for hospitals to control the hospitalization cost of hypertension. Methods: In this study, 3,595 hospitalized patients with a primary diagnosis of tertiary hypertension in Tianshui City Hospital of TCM, Gansu Province, China, from January 2017 to June 2022, were used as research subjects. Using univariate analysis to identify the relevant variables of hospitalization cost, followed by incorporating the statistically significant variables of univariate analysis as independent variables in multiple linear regression analysis, and establishing the path model based on the results of the multiple linear regression finally, to explore the factors influencing hospitalization cost comprehensively. Results: The results showed that hospitalization cost of hypertension patients were mainly influenced by length of stay, age, admission pathways, payment methods of medical insurance, and visit times, with length of stay being the most critical factor. Conclusion: The Chinese government should actively exert the characteristics and advantages of TCM in the treatment of chronic diseases such as hypertension, consistently optimize the treatment plans of TCM, effectively reduce the length of stay and steadily improve the health literacy level of patients, to alleviate the illnesses pain and reduce the economic burden of patients.

HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

HMGA1 drives chemoresistance in esophageal squamous cell carcinoma by suppressing ferroptosis.

Chemotherapy is a primary treatment for esophageal squamous cell carcinoma (ESCC). Resistance to chemotherapeutic drugs is an important hurdle to effective treatment. Understanding the mechanisms underlying chemotherapy resistance in ESCC is an unmet medical need to improve the survival of ESCC. Herein, we demonstrate that ferroptosis triggered by inhibiting high mobility group AT-hook 1 (HMGA1) may provide a novel opportunity to gain an effective therapeutic strategy against chemoresistance in ESCC. HMGA1 is upregulated in ESCC and works as a key driver for cisplatin (DDP) resistance in ESCC by repressing ferroptosis. Inhibition of HMGA1 enhances the sensitivity of ESCC to ferroptosis. With a transcriptome analysis and following-up assays, we demonstrated that HMGA1 upregulates the expression of solute carrier family 7 member 11 (SLC7A11), a key transporter maintaining intracellular glutathione homeostasis and inhibiting the accumulation of malondialdehyde (MDA), thereby suppressing cell ferroptosis. HMGA1 acts as a chromatin remodeling factor promoting the binding of activating transcription factor 4 (ATF4) to the promoter of SLC7A11, and hence enhancing the transcription of SLC7A11 and maintaining the redox balance. We characterized that the enhanced chemosensitivity of ESCC is primarily attributed to the increased susceptibility of ferroptosis resulting from the depletion of HMGA1. Moreover, we utilized syngeneic allograft tumor models and genetically engineered mice of HMGA1 to induce ESCC and validated that depletion of HMGA1 promotes ferroptosis and restores the sensitivity of ESCC to DDP, and hence enhances the therapeutic efficacy. Our finding uncovers a critical role of HMGA1 in the repression of ferroptosis and thus in the establishment of DDP resistance in ESCC, highlighting HMGA1-based rewiring strategies as potential approaches to overcome ESCC chemotherapy resistance. Schematic depicting that HMGA1 maintains intracellular redox homeostasis against ferroptosis by assisting ATF4 to activate SLC7A11 transcription, resulting in ESCC resistance to chemotherapy.

Combined effects of temperature, photoperiod, and salinity on reproduction of the brine shrimp Artemia sinica (Crustacea: Anostraca).

Background: Artemia sinica is a brine shrimp species distributed in hypersaline salt lakes in northern China and Siberia and a successful invasive species in some coastal salterns. Although it is a commercially harvested and cultured species, knowledge of its reproductive characteristics is limited, and existing studies are often contradictory. The combined effects of temperature, salinity, and photoperiod on reproduction characteristics are experimentally studied to better understand its reproductive features. Methods: There were 36 combinations of three environmental factors (3 × 3 × 4), each with three or four levels, namely temperature (16, 25, 30 °C), photoperiod (6 L:18 D, 12 L:12D, 18 L:6D), and salinity (50, 100, 150, 200 PSU). In each treatment, 48 to 80 pairs of A. sinica from Yuncheng Salt Lake (Shanxi, China) were cultured. Females were observed daily for reproductive mode and the number of offspring produced. Results: Temperature, photoperiod, salinity, and their interactions significantly affected the lifespan and reproduction of A. sinica. The reproductive period was the longest and accounted for the largest proportion of life span at moderate temperature (25 °C). Total offspring, offspring per brood, and offspring per day increased as salinity decreased, and the number of broods per female was highest at 25 °C. Temperature, photoperiod, and salinity significantly influenced reproductive modes, and interactions among these factors were identified. Artemia sinica primarily reproduces oviparously under low temperature and short daylight conditions, and ovoviviparously under high temperature and long daylight conditions, with the maximum oviparity ratio recorded in treatments of 16 °C, 6L:18D, and 50 or 100 PSU. The maximum ovoviviparity ratio was recorded under 30 °C, 12L:12D, and 100 PSU. Unlike that documented for other Artemia species or populations, the brood size of A. sinica kept increasing throughout the reproductive period. It did not decline even in the last two broods. For the same brood number, the sizes of oviparous and ovoviviparous broods were similar. The length of the oviparous interval was often greater than that of the ovoviviparous interval, suggesting that oviparous offspring might require additional energy and time to construct the multi-layered eggshell. Compared to other species and populations, the A. sinica from Yuncheng Salt Lake has a relatively shorter pre-reproductive development time, a preference for ovoviviparity, and relatively higher fecundity and population growth capacity, making it a suitable culture species for obtaining fresh biomass.

Acyclic Cucurbit[n]urils: Effective Taste Masking Nanocontainers for Cationic Bitter Compounds.

New acyclic cucurbit[n]urils (ACBs) with eight carboxylate groups were synthesized. These hosts are highly soluble in water, and can form stable inclusion complexes with cationic bitter compounds. ACBs are confirmed to be non-toxic and biocompatible. Two-bottle preference (TBP) tests on mice show that all ACBs are tasteless to mammals. ACBs are discovered to mask the bitterness of berberine and denatonium benzoate, but not quinine hydrochloride, due to different binding modes.

Metformin alleviates irradiation-induced intestinal injury by activation of FXR in intestinal epithelia.

Abdominal irradiation (IR) destroys the intestinal mucosal barrier, leading to severe intestinal infection. There is an urgent need to find safe and effective treatments to reduce IR-induced intestinal injury. In this study, we reported that metformin protected mice from abdominal IR-induced intestinal injury by improving the composition and diversity of intestinal flora. The elimination of intestinal microbiota (Abx) abrogated the protective effects of metformin on irradiated mice. We further characterized that treatment of metformin increased the murine intestinal abundance of Lactobacillus, which mediated the radioprotective effect. The administration of Lactobacillus or fecal microbiota transplantation (FMT) into Abx mice considerably lessened IR-induced intestinal damage and restored the radioprotective function of metformin in Abx mice. In addition, applying the murine intestinal organoid model, we demonstrated that IR inhibited the formation of intestinal organoids, and metformin alone bore no protective effect on organoids after IR. However, a combination of metformin and Lactobacillus or Lactobacillus alone displayed a strong radioprotection on the organoid formation. We demonstrated that metformin/Lactobacillus activated the farnesoid X receptor (FXR) signaling in intestinal epithelial cells and hence upregulated tight junction proteins and mucins in intestinal epithelia, increased the number of goblet cells, and augmented the mucus layer thickness to maintain the integrity of intestinal epithelial barrier, which eventually contributed to reduced radiation intestinal injury. In addition, we found that Lactobacillus abundance was significantly increased in the intestine of patients receiving metformin while undergoing abdominal radiotherapy and the abundance was negatively correlated with the diarrhea duration of patients. In conclusion, our results demonstrate that metformin possesses a protective effect on IR-induced intestinal injury by upregulating the abundance of Lactobacillus in the intestine.

Recent findings in Akkermansia muciniphila-regulated metabolism and its role in intestinal diseases.

The mammalian gastrointestinal tract is colonized with a majority of gut microbes, affecting host metabolism and homeostasis. Gut microbiota plays a vital role in nutrient exchange, signaling transduction between intestinal epithelial cells, and resistance to pathogen invasion. Gut microbiota is divided into mucus layer bacteria and intestinal lumen bacteria based on the colonization distribution. Akkermansia muciniphila (A. muciniphila) prefers to colonize in the intestinal mucus layer, and specifically degrades mucins to produce short-chain fatty acids, providing energy for the host and promoting colonization of the bacterium itself. Degradation of mucins prompts the host to compensate for the production of more mucins, thereby maintaining the dynamics of these proteins. In the intestinal micro-ecosystem, A. muciniphila is non-pathogenic, and its colonization with suitable abundance contributes to the development of immune system, thus promoting intestinal health. The mechanisms by which A. muciniphila bears a protective role in the host intestine are currently unclear. In this review, we summarize the microenvironment for the colonization of A. muciniphila, physiological characteristics and pathophysiological impact of A. muciniphila on intestinal diseases, such as irritable bowel syndrome, inflammatory bowel diseases, and intestinal tumors. We also provided updates for current studies on signals that A. muciniphila enhances intestinal barrier integrity and regulates immune response. Together, we conclude that A. muciniphila is a promising probiotic, which could be a microbial target for the treatment of multiple intestinal diseases.

Altered levels of circulating mitochondrial DNA in elderly people with sarcopenia: Association with mitochondrial impairment.

BACKGROUND: Age-related chronic inflammatory process is often referred to as "inflammaging", which had been described in several human disorders, including sarcopenia. Recently, mitochondrial DNA (MtDNA) has moved into the spotlight as a "damage-associated molecular pattern" (DAMP) agent that can potentially elicit inflammation. Yet, the roles of this mitochondrial DAMP have never been investigated in sarcopenia. DESIGN: Cross-sectional study. PARTICIPANTS: From January 2021 to June 2021, elderly outpatients ≥65 years and able to finish a comprehensive geriatric assessment were recruited in our study. METHODS: Participants were divided into sarcopenia group and non-sarcopenia group according to the DXA scans and grip strength. Genomic DNA was extracted from plasma and peripheral blood mononuclear cells (PBMCs), and changes in MtDNA copies were quantified using qPCR. Plasma levels of inflammatory cytokines were measured using ELISA kits. Loss of mitochondrial membrane potential (Δψm) in PBMCs was analyzed using the fluorescent probe JC-1. RESULTS: Participants with sarcopenia were significantly older, more likely to be physically inactive, and had higher levels of circulating cell-free MtDNA (ccf-MtDNA) (all p < 0.05). After adjusting for potential confounders, ccf-MtDNA was independently associated with increased odds of sarcopenia (adjusted odds ratio (AOR), 1.576; p = 0.009). Furthermore, ROC curve analysis showed that ccf-MtDNA had an area under the curve (AUC) of 0.726 (95% CI: 0.607-0.844; p < 0.05) for distinguishing elderly subjects from sarcopenia. Compared with non-sarcopenia subjects, plasma interleukin (IL)-6 and IL-8 were significantly higher in sarcopenia subjects (both p < 0.05). By performing a correlation test, it was found that the level of IL-6 was positively correlated with ccf-MtDNA (r = 0.301; p < 0.05). Then, PBMCs were used as surrogates for mitochondria-rich cells, and the results showed that the relative amplification of MtDNA in PBMCs was significantly reduced (p < 0.05), whereas the depolarization of Δψm was significantly increased in sarcopenia subjects (p < 0.05). CONCLUSIONS: Taken together, our data suggested that circulating MtDNA might be a novel and important source of inflammatory stimuli potentially relevant for sarcopenia in elderly people, and this would provide an attractive therapeutic target to improve this disease.

Lactobacillus Suppresses Tumorigenesis of Oropharyngeal Cancer via Enhancing Anti-Tumor Immune Response.

Deficiency in T cell-mediated adaptive immunity, such as low CD8+ T cell infiltration, inhibits the immune surveillance, promotes malignant transformation, and facilitates tumor growth. Microbiota dysbiosis diminishes the immune system and contributes to the occurrence of cancer. However, the impact of oral dysbiosis on the occurrence and molecular mechanisms of oropharyngeal cancer (OPC) remains largely unknown. In the current study, we used 4-nitroquinoline-1-oxide (4NQO) to mimic tobacco-related carcinogenesis to generate a murine OPC model and determine the role of microbiota changes in OPC tumorigenesis. Our results showed that the oral flora composition of mice was deregulated during the tumorigenesis of OPC. The abundance of Streptococcus, Veillonella, Muribacter, Rodentibacter, and Gemella was increased, whereas the dominant genus Lactobacillus was gradually decreased with disease progression. We further demonstrated that infiltration of CD8+ T lymphocytes was markedly reduced due to the reduction of Lactobacillus. Supplementation of Lactobacillus increased the infiltration of CD8+ T cells, promoted the expression of IFN-γ and granzyme B, and lessened the OPC progression. Analyzing the metabolites of the Lactobacillus, we demonstrated that Lactobacillus enhanced the anti-tumor immune response by producing acetate in OPC development. Administration of acetate to mice could increase the expression of IFN-γ and IFN-γ-inducible chemokines in tumor tissues by activating GPR43 to promote the infiltration of CD8+ T lymphocytes and substantially delay the development of OPC. Together, our data suggest that dysbiosis of oral microbiota promotes the tumorigenesis of OPC through downregulation of cytotoxic T lymphocytes. Lactobacillus and its metabolite acetate improve the tumor microenvironment, which could be applied in the treatment of OPC.

[Rules of acupoint selection in treatment of erectile dysfunction with acupuncture and moxibustion based on data mining technology].

Data mining technology was adopted to analyze the rules of acupoint selection in treatment of erectile dysfunction with acupuncture and moxibustion. All of the articles for acupuncture and moxibustion in treatment of erectile dysfunction were searched from the databases, i.e. Chinese national knowledge infrastructure (CNKI), Wanfang database, VIP, Chinese biomedical literature database (SinoMed) and PubMed, and the clinical trials on erectile dysfunction treated with acupuncture and moxibustion were screened. The database was set up by using Excel 2019 and input into R 4.0.3, and then, the therapeutic method, use frequency of acupoint, meridian tropism, collection visualization analysis, cluster analysis and association rule analysis were summarized. A total of 240 articles were included, with 516 prescriptions and 145 acupoints involved. The methods for treatment of erectile dysfunction included acupuncture and moxibustion therapy, acupuncture, acupoint injection, electroacupuncture, etc. The acupoints with high use frequency were Guanyuan (CV 4), Shenshu (BL 23), Sanyinjiao (SP 6), Mingmen (GV 4), Zusanli (ST 36), Zhongji (CV 3), Ciliao (BL 32), Qihai (CV 6), Taixi (KI 3) and Taichong (LR 3). The meridians involved with high frequency were the bladder meridian of foot-taiyang, the conception vessel, the spleen meridian of foot-taiyin, etc. The common acupoint combination was Shangliao (BL 31), Zhongliao (BL 33), Ciliao (BL 32), Xialiao (BL 34) and Sanyinjiao (SP 6), Shenshu (BL 23), Guanyuan (CV 4). In association rule analysis (confidence ≥ 90%, support ≥ 20%), there were 27 association rules in total. The acupoint combination with the highest support referred to "Shenshu (BL 23), Sanyinjiao (SP 6)→Guanyuan (CV 4)" (support 46.7%) and the acupoint combination with the highest confidence was "Sanyinjiao (SP 6), Qihai (CV 6)→Guanyuan (CV 4)" (confidence 98.0%). The acupoints could be divided into 5 effective clusters. Acupuncture and moxibustion therapy has a certain of rules of acupoint selection in treatment of erectile dysfunction, which provides the evidences for modern clinical trial and treatment.

Automated Cerebral Infarct Detection on Computed Tomography Images Based on Deep Learning.

The limited accuracy of cerebral infarct detection on CT images caused by the low contrast of CT hinders the desirable application of CT as a first-line diagnostic modality for screening of cerebral infarct. This research was aimed at utilizing convolutional neural network to enhance the accuracy of automated cerebral infarct detection on CT images. The CT images underwent a series of preprocessing steps mainly to enhance the contrast inside the parenchyma, adjust the orientation, spatially normalize the images to the CT template, and create a t-score map for each patient. The input format of the convolutional neural network was the t-score matrix of a 16 × 16-pixel patch. Non-infarcted and infarcted patches were selected from the t-score maps, on which data augmentation was conducted to generate more patches for training and testing the proposed convolutional neural network. The convolutional neural network attained a 93.9% patch-wise detection accuracy in the test set. The proposed method offers prompt and accurate cerebral infarct detection on CT images. It renders a frontline detection modality of ischemic stroke on an emergent or regular basis.

Fissistiganoids A and B: two new flavonoids from the Fissistigma tungfangense.

Two new flavanoids fissistiganoids A and B (1 and 2), together with two known pterocarpans derivatives (3 and 4), were isolated from the stems of Fissistigma tungfangense. The structures of these compounds were elucidated using comprehensive spectroscopic methods. The absolute configurations of fissistiganoids A and B (1 and 2) were determined by comparing their ECD spectra with quantum-mechanics ECD calculations. The inhibitory activities of all compounds against three cancer cell lines HeLa, MCF-7 and A549 were evaluated. Compounds 1-4 showed moderate inhibitory effects on HeLa, MCF-7 and A549 cells with IC50 values ranging from 12.5 to 42.3 µM.

Seed oil of Brucea javanica induces apoptosis through the PI3K/Akt signaling pathway in acute lymphocytic leukemia Jurkat cells.

Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3ß was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.

[Study on secondary metabolites of endophytic fungus Cladosporium sp. JJM22 hosted in Ceriops tagal].

Nine secondary metabolites(S)-5-hydroxy-4-methylchroman-2-one(1), 4-methoxynaphthalene-1,5-diol(2), 8-methoxynaphthalene-1,7-diol(3), 1,8-dimethoxynaphthalene(4),(2R,4S)-2,3-dihydro-2-methyl-benzopyran-4,5-diol(5),(2R,4R)-3,4-dihydro-4-methoxy-2-methyl-2H-1-benzopyran-5-ol(6), 7-O-α-D-ribosyl-2,3-dihydro-5-hydroxy-2-methyl-chromen-4-one(7),(R)-3-methoxyl-1-(2,6-dihydroxyphenyl)-butan-1-one(8) and helicascolide A(9) were isolated from endophytic fungus Cladosporium sp. JJM22 by using column chromatographies of silica gel and ODS, and semi-preparative HPLC. Their structures were analyzed on the basis of spectroscopic and chemical data, especially NMR and MS. All isolated compounds were evaluated for their anti-inflammatory activities by examining the inhibitory activities on nitric oxide(NO) production induced by lipopolysaccharide in mouse macrophage RAW264.7 cells in vitro. Compounds 2-4 showed inhibitory activities.

Five New Triene Derivatives from the Fungus Penicillium herquei JX4.

Five undescribed triene derivatives, pinophols B-F (2-6), together with one known compound, pinophol A (1), were obtained from the mangrove endophytic fungus Penicillium herquei JX4. The structures of compounds 1-6 were elucidated using IR, HR-ESI-MS, and NMR methods. The absolute configurations of compounds 1-6 were confirmed by comparing their experimental or calculated ECD spectra. Pinophols C and D (3 and 4) showed inhibitory activities against LPS-induced NO production.

Multiset Feature Learning for Highly Imbalanced Data Classification.

With the expansion of data, increasing imbalanced data has emerged. When the imbalance ratio (IR) of data is high, most existing imbalanced learning methods decline seriously in classification performance. In this paper, we systematically investigate the highly imbalanced data classification problem, and propose an uncorrelated cost-sensitive multiset learning (UCML) approach for it. Specifically, UCML first constructs multiple balanced subsets through random partition, and then employs the multiset feature learning (MFL) to learn discriminant features from the constructed multiset. To enhance the usability of each subset and deal with the non-linearity issue existed in each subset, we further propose a deep metric based UCML (DM-UCML) approach. DM-UCML introduces the generative adversarial network technique into the multiset constructing process, such that each subset can own similar distribution with the original dataset. To cope with the non-linearity issue, DM-UCML integrates deep metric learning with MFL, such that more favorable performance can be achieved. In addition, DM-UCML designs a new discriminant term to enhance the discriminability of learned metrics. Experiments on eight traditional highly class-imbalanced datasets and two large-scale datasets indicate that: the proposed approaches outperform state-of-the-art highly imbalanced learning methods and are more robust to high IR.

Pseudoginsenoside-F11 attenuates cognitive dysfunction and tau phosphorylation in sporadic Alzheimer's disease rat model.

We previously reported that pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, significantly ameliorated Alzheimer's disease (AD)-associated cognitive defects in APP/PS1 and SAMP8 mice by inhibiting Aß aggregation and tau hyperphosphorylation, suggesting a potential therapeutic effect of PF11 in the treatment of AD. In the present study we further evaluated the therapeutic effects of PF11 on relieving cognitive impairment in a rat model of sporadic AD (SAD). SAD was induced in rats by bilateral icv infusion of streptozotocin (STZ, 3 mg/kg). The rats were treated with PF11 (2, 4, 8 mg·kg-1·d-1, ig) or a positive control drug donepezil (5 mg·kg-1·d-1, ig) for 4 weeks. Their cognitive function was assessed in the nest building, Y-maze, and Morris water maze tests. We showed that STZ icv infusion significantly affected the cognitive function, tau phosphorylation, and insulin signaling pathway in the hippocampus. Furthermore, STZ icv infusion resulted in significant upregulation of the calpain I/cyclin-dependent protein kinase 5 (CDK5) signaling pathway in the hippocampus. Oral administration of PF11 dose-dependently ameliorated STZ-induced learning and memory defects. In addition, PF11 treatment markedly reduced the neuronal loss, protected the synapse structure, and modulated STZ-induced expression of tau phosphorylation by regulating the insulin signaling pathway and calpain I/CDK5 signaling pathway in the hippocampus. Donepezil treatment exerted similar beneficial effects in STZ-infused rats as the high dose of PF11 did. This study highlights the excellent therapeutic potential of PF11 in managing AD.

Pinocembrin Ameliorates Cognitive Impairment Induced by Vascular Dementia: Contribution of Reelin-dab1 Signaling Pathway.

BACKGROUND: As a substrate of apoER2, Reelin has been verified to exert neuroprotection by preventing memory impairment. Pinocembrin is the most abundant natural flavonoid found in propolis, and it has been used to exert neuroprotection, blood-brain barrier protection, anti-oxidation, and inflammation diminishing, both in vitro and in vivo. However, the roles and molecular mechanisms of pinocembrin in neurobehavioral outcomes and neuronal repair after vascular dementia are still under investigation. PURPOSE: To explore the role of pinocembrin in the involvement of the Reelin-dab1 signaling pathway in improving memory impairment, both in cell culture and animals experiments. MATERIAL AND METHODS: Behavioral tests were conducted on day 48 to confirm the protection of pinocembrin against cognitive impairment. Cell and molecular biology experiments demonstrated that the Reelin-dab1 pathway mediates the underlying mechanism of cognitive improvement by pinocembrin. RESULTS: It was showed that pinocembrin alleviated learning and memory deficits induced by vascular dementia, by inducing the expression of Reelin, apoER2, and p-dab1 in the hippocampus. The expression of Reelin and p-dab1 was both inhibited following Reelin RNA interference in SH-SY5Y prior to oxygen glucose deprivation (OGD) injury, suggesting that Reelin played a core role in pinocembrin's effect on OGD in vitro. CONCLUSION: Pinocembrin improves the cognition via the Reelin-dab1 signaling pathway.

[Material basis and molecular mechanism of Dachengqi Decoction in treatment of acute pancreatitis based on network pharmacology].

The network pharmacology was used to investigate the material basis and molecular mechanism of Dachengqi Decoction(DCQD) in the treatment of acute pancreatitis(AP). Potential targets of components from DCQD and relevant pathogenic genes of AP were identified through database retrieval. Then, crucial targets were verified with relevant active chemical components via molecular docking. DAVID database was used to explore the functions and pathways involved in the treatment of AP. A total of 108 components were correlated with 28 targets. Molecular docking showed a strong binding ability of key targets and their corresponding compounds. DAVID enrichment analysis showed 438 biological process, 31 molecular functions, 17 cellular components and 96 KEGG pathways. DCQD may achieve its pharmacological effects through anti-inflammatory and anti-oxidative effects, negative regulation of apoptosis and regulation of pancreatic secretion, involving multiple signals, such as IL-17, TNF and NF-κB signaling pathway. In this study, it is the first time to use the method of network pharmacology to reveal the molecular mechanism of DCQD in the treatment of AP by multiple components and multi-signaling pathways, which provides a basis for further biological experiments of AP.